The list of available chiral ligands for asymmetric catalytic transformations continues to grow at a rapid pace, and yet many desirable reactions remain impractical due to the limitations of currently available catalyst systems. In particular, achieving both high rates and high enantio selectivities in catalysis remains a serious challenge that continues to present the principal obstacle to the development of cost-effective asymmetric catalytic processes.
Burk, in Handbook of Chiral Chemicals, ed. Ager, Marcel Dekker, Inc., New York (1999), Chapter 18: 339-59, and references cited therein, reports that ligands composed of 2,5-disubstituted phospholane groups may bestow significant advantages in terms of enantioselectivities in asymmetric catalytic hydrogenation reactions. Unfortunately, catalysts that rendered the highest selectivities (e.g. DuPHOS-Rh and BPE-Rh) often displayed low catalytic rates in the hydrogenation of certain functional groups (e.g. ketones, hindered alkenes, etc.). Burk and Gross, Tet. Lett. 35:9363 (1994), report that reaction rates could be accelerated by the introduction of more flexible ligand backbones (e.g. 1,3-propano and 1,1'-ferrocenyl bridges), but enantioslectivities fell.
WO-A-98/02445 describes chiral phosphetane ligands as defined by general formula 1, or the opposite enantiomer thereof, wherein R groups are each independently H, alkyl, cycloalkyl, aryl or alkaryl, provided that R.sup.1 and R.sup.2 are both not H, and X is any group capable of forming a stable bond to phosphorus. In particular, WO-A-98/02445 highlights the synthetic utility of rhodium complexes of monophosphetanes of formula 2, wherein R.sup.1.dbd.R.sup.2, in comparison with five-membered ring analogues of formula 3 ##STR2##
WO-A-99/02444 (published after the priority dates claimed in this Application) describes an improved process for the preparation of cyclic phosphines. This involves the addition of strong base to a preformed mixture or reaction product of a primary phosphine and an alkylating agent.